Ortho-hydroxy-benzylamine arsonic acids and process of making same



Patented Dec. 8, 1931 UNITED STATES PATENT OFFICE WERNER SCHMIDT, OF FRANKFORT ON-THE-MAIN/MAINKUR, GERMANY, ASSIGNOR 'IO WINTHROIP CHEMICAL COMPANY, INC., OF NEW YORK, N. Y., A CORPORATION OF NEW YORK ORTHO-HYDROXY-BENZYLAMINE ARSONIG ACIDS AND PROCESS OF MAKING SAME No Drawing. Application filed. May 22, 1928, Serial No. 279,854, and in Germany May 31, 1927.

The present invention relates to new orthohydroXy-benzyl-amine arsonic acids and to a process of preparing the same.

I have found that new ortho-hydroxybenzylamine arsonic acids of the general formula:

wherein Y stands for hydrogen or methyl, are obtained by diazotizing 1-amino-4-hydroXy-5-benzyl-aroyl-amines of the general formula:

Y OHPI'Q -O f wherein the Xs stand for hydrogen atoms which may be jointly replaced by a @0- group, and Y has the aforesaid'signification, acting on the diazocompounds thus formed with an alkali arsenite in an alkaline solution and treating the 4-hydroXy-5-benzyl-aroyl- 3o amine-l-arsonic acids thus obtained with saponifying agents.

The 1 amino 4- hydroxy 5 -benzyl-aroylamines used as starting materials for my process may be prepared by condensing paranitrophenol compounds with hydroxymethyl-aroyl-aminesandreducingthel-nitro- 4 hydroxy 5 benzyl aroyl amines thus formed as described by Einhorn in Liebigs Annalen, vol. 343, page 223.

7 1o Onev may proceed also in such a manner,

that 4 hydroXy-5-benzyl-aroyl-amine-l-arsonic acids are produced according to my copending application SerialNo. 279,855, filed May 22 1928, and are treated subsequently with saponifying agents.v

The new compounds obtained by my process possess a good therapeutical activity and are of an especial importance because they lack any neurotoxic action. They may also be used as starting materials for manufacturing other pharmaceutical products.

In order to further illustrate myinvention the following examples are given, the parts being by weight and all temperatures in Centigrade degrees; but I wish to be understood that my invention is not limited to the examples given, nor' to the exact conditions stated therein. 7

Example 1 (a) Manufacture of the 4-hydroxy-5-benzyl-benzoylamine-l-arsonic acid of the formula: I

24,2 parts of 1-amino-4-hydroXy-5-benzylbenzoylamine, described by Einhorn in Liebigs Annalen, vol. 343, page 248, are suspended in 200 parts of water and 200 parts of ice with the addition of 32 parts of hydrochloric acid (cZ=1,185) and diazotized at 0-5 by means of a solution of 7 parts of sodium nitrite in 20 parts of water. The diazocompound thus obtained is allowed to run while well stirring into a mixture of 150 When the and precipitating the filtrated solution by means of hydrochloric acid. It is identical with the compound described in the Example 1 of my copending U. S. application Serial No. 279,855, filed May 22, 1928.

(b) Manufacture of the 4-hydroxy-5-benzylamine-l-arsonic acid of the formula:

OCHPNHR l AsOaHz 25 parts of 4-hydroxy-5-benzyl-benzoylamine-l-arsonic acid prepared as described sub-paragraph (a) or according to my copending application are boiled under a reflux condenser with 100 parts of water and 60' parts of a caustic soda solution of 33 Be for about 5 hours. Then the mass is diluted with 100 parts of water filtered in the cold and mixed with 90 parts of hydrochloric acid (d=1,15).' After cooling down to 0 the precipitated benzoic acid is filtered off. The filtrate thereof is warmed at about 75 and neutralized with sodium acetate. From this solution the new compound crystallizes in the form of fine needles melting above 290. It is easily soluble in dilute mineral acids, in alkalies and in solutions of alkali carbonates, difliculty soluble in a solution containing an excess of sodium acetate, in acetone, methylalcohol and ethylalcohol, insoluble in ether, benzene and benzine.

Example 2 ((1) Manufacture of 1-amino-4 -hydroxy-5- benzyl-phthalic imide of the formula:

CHz-N I 00 OCH,N COQ It is nearly insoluble inwater, clifficultly soluble in alkalies forming a yellow solution. By

reducing it with iron and acetic acid the new 1-amino-l-hydroxy-5-benzyl phthalic imide is obtained. This base crystallizes from a mixture of methanol and ether in the form of colorless needles melting at 9597, it is easily soluble in alcohol, difiicultly soluble in water, insoluble in ether.

(7)) Manufacture of the 4-hydroxy-5-benzyl phthalic imide-l-arsonic acid of the formula:

oocHN JLSOsHz reaction product is separated by the addition 9 of common salt. It is purified by extracting with acetone and then with a small quantity of spirit. The residue therefrom is dissolved in a sodium acetate solutionand after having been decolorized by means of animal charcoal the solution is precipitated by addition of an acid.

The compound thus obtained is identical with the 4-hydroxy-5-benzyl-phthalic-imidel-arsonic acid described in the Example 2 of my copending U. S. application Serial No. 279,855, filed May 22, 1928. It yields when saponified according to the foregoing example sub-paragraph (b), the same hydroxybenzylamine arsonic acid as there described.

Example 3 When starting from 800 parts of paranitro-cresol of the formula:

and of the melting point 95 and working otherwise as described in Example 2, the 4 hydroxy 3-methyl-5benzyl phthalidimide-L arsonic acid is obtained. It is identical to the compound described in Example 4 of the copending application executed by me on the same date. By means of saponifying agents it yields the l-hydroxy-S-methyh 5-benzylamine-l-arsonic acid of the formula:

l ASOaHz This product melts above 290 it is easily soluble in alkalies and in dilute mineral acids, diflicultly soluble in-an alkali acetate solution and in spirit, insoluble in ether, benzene and benzine.

I claim:

1. Process for manufacturing ortho-hydroXy-benzylamine arsonic acids which process comprises diazotizing l-amino-l-hydroxy- 5-benzyl-aroylamines of the general formula:

Y- C Hz-lTl-C O formula Y era-l ve o X X A30 aHz wherein the Xs stand for hydrogen atoms which may be jointly replaced by a CO-group and Y stands for hydrogen or methyl, with saponifying agents.

3. As new products ortho-hydroxy-benzylamine-arsenic acids of the general formula:

l AS O 3112 wherein Y stands for hydrogen or the methyl group, which products are colorless crystalline substances, having a definite melting point, difficultly soluble in organic solvents, easily soluble in mineral acids and in alkaline agents.

4. As a new product the 4-hydr0Xy-5-benzylamine-l-arsonic acid of the formula:

CHr-NHa which product represents fine needles melting above 290 0., easily soluble in dilute mineral acids, in alkalies and in solutions of alkali carbonates, diflicultly soluble in a solution of excessive alkali acetate, in acetone, methyl and ethyl alcohol, insoluble in ether, benzene and benzine.

In testimony whereof, I aflix my signature.

WERNER SCHMIDT.

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